posted on 2023-01-12, 13:06authored byThomas Duhamel, Simone Scaringi, Baptiste Leforestier, Amalia I. Poblador-Bahamonde, Clément Mazet
Two complementary regiodivergent Pd-catalyzed assisted
tandem [isomerization/Heck
arylation] reactions are reported. They provide access to a broad
array of acyclic trisubstituted vinyl ethers starting from readily
available alkenyl ethers. In both cases, the isomerization is conducted
with a [Pd–H] precatalyst supported by tris-tert-butyl phosphine ligands. When the catalyst is modified by the addition
of a chelating bisphosphine ligand (dppp), an organic base (Cy2NMe), sodium acetate, and aryl triflates are used as electrophiles,
the α-arylation pathway is promoted preferentially. The β-arylation
pathway is favored for electron-deficient and electron-neutral aryl
halides when the catalyst is simply modified by the addition of an
excess of an organic base (Et3N) after completion of the
isomerization reaction. Electron-rich aryl halides lead to reduced
levels of regiocontrol. The moderate stereoselectivity obtained are
proposed to reflect the absence of stereocontrol in the isomerization
step. Computational analyses suggest that migratory insertion is selectivity-determining
for both the arylations. For the β-selective arylation, an energy
decomposition analysis underscored that electronic factors favor α-regioselectivity
and steric effects favor β-regioselectivity. Preliminary investigations
show that high levels of stereoselectivity can be achieved for the
α-selective arylation by ligand control. Complementarily, reaction
conditions for postcatalytic stereo-correction have also been identified
for each catalytic system.